Is MYO7A p.Pro1617= (c.4851C>T) pathogenic?

MYO7A p.Pro1617= (c.4851C>T) is classified Conflicting classifications of pathogenicity in MYO7A (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2022-08-31). Very rare (popmax 0.00342%, sas); Associated with Usher syndrome type 1B.

What condition is associated with MYO7A p.Pro1617= (c.4851C>T)?

MYO7A p.Pro1617= (c.4851C>T) is associated with Usher syndrome type 1B (ClinVar).

How common is MYO7A p.Pro1617= (c.4851C>T) in the general population?

MYO7A p.Pro1617= (c.4851C>T) is very rare (popmax 0.00342%, sas) (gnomAD).

MYO7A p.Pro1617=

c.4851C>T · rs372535399 · VCV178488

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00342%, sas)

Conditions

Usher syndrome type 1B

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.36 · evaluated, not missing
Constraint at this position
Conservation	phyloP -1.2	GERP -3.3, phastCons 0.001
Overall
CADD	7.817	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00342% South Asian · 3/87,776 alleles

Filtering AF 0.00132% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0011%

Overall 0.00177% 28/1,582,286 alleles · very rare exomes 25/1,430,076 · genomes 3/152,210 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00342%	29,259
European (non-Finnish)	0.00199%	50,354
Admixed American	0.0017%	58,784
African / African-American	0.00134%	74,512

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: MYO7A
Protein: p.Pro1617=
Coding: c.4851C>T
MANE Select: NM_000260
dbSNP: rs372535399
Type: single nucleotide variant
Location: chr11:77199817 (GRCh38)
Gene constraint: LOEUF 0.995 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73 · 1 PDB
Residue 1617: the sh3 domain

Full MYO7A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Usher syndrome type 1B — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MYO7A p.Pro1617Leu Uncertain significance ★★ ⚠ same residue
MYO7A p.Ala1288Pro Likely pathogenic ★★★ same condition
MYO7A p.Arg1168Gln Pathogenic ★★★ ⚠ same condition
MYO7A p.Arg1873Gln Pathogenic ★★★ ⚠ same condition
MYO7A p.Arg395Cys Likely pathogenic ★★★ ⚠ same condition
MYO7A p.Arg668Cys Pathogenic ★★★ same condition
MYO7A p.Arg853His Likely pathogenic ★★★ same condition
MYO7A p.Glu968Asp Likely pathogenic ★★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/myo7a-p-pro1617 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown